tbuckley/cabot-search huggingface dataset:
Selected Articles from This Issue
Journal: Clinical Cancer Research (2020)

Aapalutamide is an orally administered selective androgen receptor inhibitor.In a post-hoc analysis of the SPARTAN study, Perez-Ruixo and colleagues assessed the relationships between exposure to apalutamide and its active metabolite, N-desmethyl-apalutamide, with clinical efficacy and safety endpoints.A total of 21% of patients receiving apalutamide experienced dose reductions diminishing the average daily dose to 209 mg instead of 240 mg.Differences in apalutamide and N-desmethyl-apalutamide exposures after the administration of apalutamide dose of 240 mg once daily did not result in clinically relevant differences in metastasisfree survival.Skin rash and weight loss were significantly associated with apalutamide exposure, with patients who had higher exposures being more likely to experience these adverse events.These results indicate that patients experiencing adverse events linked to apalutamide treatment may benefit from dose-reduction without compromising treatment efficacy.
Endoscopy International Open – recently published
Journal: Endoscopy (2020)

Comment on: Endoscopic ultrasound-guided hepaticogastrostomy or hepaticojejunostomy without dilation using a stent with a thinner delivery systemEndosc Int Open 2020; 08(08): E1034-E1038DOI: 10.1055/a-1169-3749 Comment on: The pocket-creation method may facilitate endoscopic submucosal dissection of large colorectal sessile tumorsEndosc Int Open 2020; 08(08): E1021-E1030DOI: 10.1055/a-1190-7880 Comment on: Feasibility of Speedboat RS2 with bipolar radiofrequency energy for peroral endoscopic myotomy in patients with achalasia (with video)Endosc Int Open 2020; 08(08): E998-E1001DOI: 10.1055/a-1165-0087
Selected Articles from This Issue
Journal: Clinical Cancer Research (2020)

No prior therapy with AA-P or ENZ Prior therapy with AA-P or ENZ AA-P ENZ AA-P & ENZ Prior therapy with taxanes Prior therapy with taxanes Ongoing on treatment PSA progression Ongoing on treatment PSA progression Time (days) Time (days) A B Posadas et al. | Page 3517 Apalutamide, a next-generation androgen receptor (AR) inhibitor, is currently approved for patients with both nonmetastatic and metastatic castration-resistant prostate cancer (mCRPC) receiving androgen deprivation therapy.However, the combination of apalutamide and AR signaling inhibitors, such as abiraterone acetate, in CRPC has not been studied extensively.Posadas and colleagues conducted a phase Ib study to evaluate the pharmacokinetics, safety, and antitumor activity of apalutamide combined with abiraterone acetate and prednisone (AA-P) in patients with mCRPC.No significant pharmacokinetic interaction was observed between apalutamide and abiraterone; however, treatment with apalutamide decreased exposure to prednisone.Treatment with apalutamide plus AA-P was well tolerated, with evidence of antitumor activity in patients with late-stage disease, including those who have disease progression while taking AR signaling inhibitors.These results support further clinical development of this combination in patients with mCRPC.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

Blocking Tregs in Cancer, the SAGA Continues Regulatory T cells (Tregs) suppress antitumor immunity.Cortez and colleagues used a pooled CRISPR screen in primary mouse regulatory T cells to identify regulators of Foxp3, the master transcription factor required for Treg function.They identified regulators of chromatin ubiquitination, members of the deubiquitinase (DUB) module of the SAGA chromatin-modifying complex (ubiquitin-specific peptidase 22-Usp22 and Ataxin-7-like 3-Atxn7l3), as critical for Foxp3 expression.Conversely, a reciprocally acting E3 ubiquitin ligase, ring finger protein 20 (Rnf20), negatively regulated Foxp3 expression.Deletion of Usp22 specifically in Tregs reduced expression of Foxp3 and diminished capacity to control autoimmunity in vivo.In multiple models of cancer, deletion of Usp22 in Tregs led to improved tumor control via increased infiltration by functional CD8 þ T cells.Mechanistically, in the absence of Usp22 (versus Rnf20 knock out Tregs), there was increased ubiquitination of H2BK120, a mark associated with gene silencing, across the genome and specifically at the Foxp3 locus.Expert Commentary: Targeting the histone deubiquitinase Usp22 disrupts Treg function and enhances antitumor immunity.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2020)

Leptomeningeal carcinomatosis (LC) from breast cancer is a disabling condition resulting from rapid and expansive tumor growth along the meningeal membranes.ANG1005 consists of three paclitaxel molecules covalently linked to Angiopep-2, designed to cross the blood-brain and blood-cerebrospinal barriers.Kumthekar and colleagues performed a phase II study of ANG1005 in breast cancer patients with brain metastases with or without LC.ANG1005 was observed to cross the blood-brain barrier to reach tumor cells.Stable disease or better was seen in the majority of the evaluable patients, with iORR of 15% (investigator) or 8% (independent radiology review).In the LC subset, 79% of the patients had intracranial disease control with an estimated median overall survival of 8.0 months (95% CI, 5.4-9.4).A randomized phase III trial of this agent is currently underway to further assess its efficacy in patients with LC.
Endoscopy International Open – recently published
Journal: Endoscopy (2020)

Comment on:Rendezvous transgastric and percutaneous sinus tract endoscopy (STE) for debridement of necrotic collections with deep retroperitoneal extension: a case series (with video)Endosc Int Open 2020; 08(05): E668-E672DOI: 10.1055/a-1134-4786Comment on:Endoscopic full-thickness resection of early colorectal neoplasms using an endoscopic submucosal dissection knife: a retrospective multicenter studyEndosc Int Open 2020; 08(05): E611-E616DOI: 10.1055/a-1127-3092Comment on:First-in-man feasibility study of a novel ingestible magnetically inflated balloon capsule for treatment of obesityEndosc Int Open 2020; 08(05): E607-E610DOI: 10.1055/a-1127-2991
Selected Articles from This Issue
Journal: Clinical Cancer Research (2020)

Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia (ALL).Burke and colleagues conducted a pilot clinical trial in patients with ALL using two classes of epigenetic modifying agents (decitabine and vorinostat) with the goal of synergistically targeting epigenetic alterations before and during chemotherapy that included UK ALLR3 reinduction.On this regimen, nine subjects (39%) achieved a complete response and five had stable disease (22%).Modulation of epigenetic marks was observed.However, the toxicity profile of the combination assessed was not acceptable.Therefore, future studies are necessary to determine if epigenetic modifying therapies can be successfully combined with chemotherapeutics for children with relapsed leukemia.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

Mechanism of Tumor Formation in ACVR1 Mutant DIPGTwenty percent of diffuse intrinsic pontine glioma (DIPG) harbor ACVR1 mutations.Fortin and colleagues expressed Acvr1 G328V in the ventral pons through an Olig2-Cre mouse.The resulting Acvr1 floxG328V/þ ; Olig2 Cre/þ mice died early with neurological signs, hyperactive BMP signaling, proliferation of oligodendrocyte precursor cells (OPC), inhibition of oligodendrocyte differentiation, and upregulation of the OPC marker PDGFRA.Knock-in of an endogenous Hist1h3b K27M allele induced BMP target genes through K27me3 hypomethylation but was insufficient to drive tumor formation.Introduction of a PIK3CA mutation, observed commonly in DIPG in combination with ACVR1 G328V and Hist1h3b K27M , resulted in high-grade diffuse glioma, with elevated expression of genes seen with Acvr1 floxG328V/þ alone, specifically ASCL1, SOX11, and ID1/2/3.Treatment with E6201, a dual inhibitor of ACVR1 and MEK1, prolonged survival.
Editorial Board and Contents
Authors: Travis Ingram, Jack Da Silva, Jacob Moorad, Daniel Promislow, Jonathan Forum, Federico López-Osorio, Yannick Wurm, Chuliang Song, Sarah Ahn, Rudolf Rohr, Serguei Saavedra, Bernard Piette, Jonathan Heddle, Mary Ruckelshaus, Stephen Jackson, Harold Mooney, Katharine Jacobs, Karim-Aly Kassam, Mary Arroyo, András Báldi, Ann Bartuska, James Boyd, Lucas Joppa, Anikó Kovács-Hostyánszki, Jill Parsons, Robert Scholes, Jason Shogren, Zhiyun Ouyang, Stacey Smith, Matthew Pennell, Casey Dunn, Scott Edwards, Andrea Stephens, Jessica Miles, Margriet Ten Napel, Patrick Scheffmann, Göran Arnqvist, Spencer Barrett, Ragan Callaway, Stephen Carpenter, James Clark, Paul Craze, Rodolfo Dirzo, Andrew Dobson, Michael Donoghue, Douglas Erwin, Bernie Boutin
Journal: Trends in Ecology & Evolution (2020)
A pathogenic integrated view explaining the different endotypes of asthma and allergic disorders
Authors: Enrico Maggi, Paola Parronchi, Bruno Giuseppe Azzarone, Lorenzo Moretta
Journal: Allergy (2022)

The inflammation of allergic diseases is characterized by a complex interaction between type 2 and type 3 immune responses, explaining clinical symptoms and histopathological patterns. Airborne stimuli activate the mucosal epithelium to release a number of molecules impacting the activity of resident immune and environmental cells. Signals from the mucosal barrier, regulatory cells, and the inflamed tissue are crucial conditions able to modify innate and adaptive effector cells providing the selective homing of eosinophils or neutrophils. The high plasticity of resident T- and innate lymphoid cells responding to external signals is the prerequisite to explain the multiplicity of endotypes of allergic diseases. This notion paved the way for the huge use of specific biologic drugs interfering with pathogenic mechanisms of inflammation. Based on the response of the epithelial barrier, the activity of resident regulatory cells, and functions of structural non-lymphoid environmental cells, this review proposes some immunopathogenic scenarios characterizing the principal endotypes which can be associated with a precise phenotype of asthma. Recent literature indicates that similar concepts can also be applied to the inflammation of other non-respiratory allergic disorders. The next challenges will consist in defining specific biomarker(s) of each endotype allowing for a quick diagnosis and the most effective personalized therapy.
Amorphous Precursor‐Mediated Calcium Phosphate Coatings with Tunable Microstructures for Customized Bone Implants
Authors: Li‐Na Wang, Yu‐Feng Meng, Yanhuizhi Feng, Hai‐Cheng Wang, Li‐Bo Mao, Shu‐Hong Yu, Zuo‐Lin Wang
Journal: Advanced Healthcare Materials (2022)

Calcium phosphate (CaP) is frequently used as coating for bone implants to promote osseointegration. However, commercial CaP coatings via plasma spraying display similar microstructures, and thus fail to provide specific implants according to different surgical conditions or skeletal bone sites. Herein, inspired by the formation of natural biominerals with various morphologies mediated by amorphous precursors, CaP coatings with tunable microstructures mediated by an amorphous metastable phase are fabricated. The microstructures of the coatings are precisely controlled by both polyaspartic acid and Mg2+ . The cell biological behaviors, including alkaline phosphatase activity, mineralization, and osteogenesis-related genes expression, on the CaP coatings with different microstructures, exhibit significant differences. Furthermore, in vivo experiments demonstrate the osseointegration in different types of rats and bones indeed favors different CaP coatings. This biomimetic strategy can be used to fabricate customized bone implants that can meet the specific requirements of various surgery conditions.
Urticaria and/or angioedema secondary to <scp>mRNA COVID</scp>‐19 vaccines: Updates from a United States case registry
Authors: Sara Anvari, Upeka Samarakoon, Xiaoqing Fu, Jordan Jaggers, Alexei Gonzalez‐Estrada, Hey Jin Chong, Sara W. Van Meerbeke, Andrej A. Petrov, David A. Khan, Esther E. Freeman, Aleena Banerji, Kimberly G. Blumenthal
Journal: Allergy (2022)
Engineered bispecific antibodies targeting the interleukin-6 and -8 receptors potently inhibit cancer cell migration and tumor metastasis
Authors: Huilin Yang, Michelle N. Karl, Wentao Wang, Bartholomew Starich, Haotian Tan, Ashley Kiemen, Alexandra B. Pucsek, Yun-Huai Kuo, Gabriella C. Russo, Tim Pan, Elizabeth M. Jaffee, Elana J. Fertig, Denis Wirtz, Jamie B. Spangler
Journal: Molecular Therapy (2022)

Simultaneous inhibition of interleukin-6 (IL-6) and interleukin-8 (IL-8) signaling diminishes cancer cell migration, and combination therapy has recently been shown to synergistically reduce metastatic burden in a preclinical model of triple-negative breast cancer. Here, we have engineered two novel bispecific antibodies that target the IL-6 and IL-8 receptors to concurrently block the signaling activity of both ligands. We demonstrate that a first-in-class bispecific antibody design has promising therapeutic potential, with enhanced selectivity and potency compared with monoclonal antibody and small-molecule drug combinations in both cellular and animal models of metastatic triple-negative breast cancer. Mechanistic characterization revealed that our engineered bispecific antibodies have no impact on cell viability, but profoundly reduce the migratory potential of cancer cells; hence they constitute a true anti-metastatic treatment. Moreover, we demonstrate that our antibodies can be readily combined with standard-of-care anti-proliferative drugs to develop effective anti-cancer regimens. Collectively, our work establishes an innovative metastasis-focused direction for cancer drug development. Simultaneous inhibition of interleukin-6 (IL-6) and interleukin-8 (IL-8) signaling diminishes cancer cell migration, and combination therapy has recently been shown to synergistically reduce metastatic burden in a preclinical model of triple-negative breast cancer. Here, we have engineered two novel bispecific antibodies that target the IL-6 and IL-8 receptors to concurrently block the signaling activity of both ligands. We demonstrate that a first-in-class bispecific antibody design has promising therapeutic potential, with enhanced selectivity and potency compared with monoclonal antibody and small-molecule drug combinations in both cellular and animal models of metastatic triple-negative breast cancer. Mechanistic characterization revealed that our engineered bispecific antibodies have no impact on cell viability, but profoundly reduce the migratory potential of cancer cells; hence they constitute a true anti-metastatic treatment. Moreover, we demonstrate that our antibodies can be readily combined with standard-of-care anti-proliferative drugs to develop effective anti-cancer regimens. Collectively, our work establishes an innovative metastasis-focused direction for cancer drug development.
Polymer-coated BiOCl nanosheets for safe and regioselective gastrointestinal X-ray imaging
Authors: I.V. Zelepukin, I.N. Ivanov, A.B. Mirkasymov, K.G. Shevchenko, A.A. Popov, P.N. Prasad, A.V. Kabashin, S.M. Deyev
Journal: Journal of Controlled Release (2022)
The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs—Part A: Renal, Penile, and Testicular Tumours
Authors: Holger Moch, Mahul B. Amin, Daniel M. Berney, Eva M. Compérat, Anthony J. Gill, Arndt Hartmann, Santosh Menon, Maria R. Raspollini, Mark A. Rubin, John R. Srigley, Puay Hoon Tan, Satish K. Tickoo, Toyonori Tsuzuki, Samra Turajlic, Ian Cree, George J. Netto
Journal: European Urology (2022)

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour".
Corrigendum to “Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers” [Semin. Cancer Biol. 83 (2022) 556–569]
Authors: Kuo Chen, Pengwei Lu, Narasimha M Beeraka, Olga A Sukocheva, SubbaRao V Madhunapantula, Junqi Liu, Mikhail Y Sinelnikov, Vladimir N Nikolenko, Kirill V Bulygin, Liudmila M Mikhaleva, Igor V Reshetov, Yuanting Gu, Jin Zhang, Yu Cao, Siva G Somasundaram, Cecil E Kirkland, Ruitai Fan, Gjumrakch Aliev
Journal: Seminars in Cancer Biology (2022)
Gene-guided OX40L anchoring to tumor cells for synergetic tumor “self-killing” immunotherapy
Authors: Lin Lin, Yingying Hu, Zhaopei Guo, Jie Chen, Pingjie Sun, Huayu Tian, Xuesi Chen
Journal: Bioactive Materials (2022)

The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade (ICB) therapy. Here, a tumor "self-killing" therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy. We developed a highly efficient delivery system HA/PEI-KT (HKT) to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide (CpG). On the one hand, CpG induced the expression of OX40 on T cells within tumors. On the other hand, OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis. Such synergistic tumor "self-killing" strategy finally turned "cold" tumors to "hot", to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) blockade therapy, and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models, with prevention of tumor recurrence and metastasis. To avoid the side effects, the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy, which showed negligible toxicity in vivo. Our work provided a new possibility for tumor "self-killing" immunotherapy to treated various solid tumors.
SARS-CoV-2 and the central nervous system: Emerging insights into hemorrhage-associated neurological consequences and therapeutic considerations
Authors: Joy Mitra, Manohar Kodavati, Vincent E. Provasek, K.S. Rao, Sankar Mitra, Dale J. Hamilton, Philip J. Horner, Farhaan S. Vahidy, Gavin W. Britz, Thomas A. Kent, Muralidhar L. Hegde
Journal: Ageing Research Reviews (2022)
Characteristics of Older Patients With Immunotolerant Chronic Hepatitis B Virus Infection
Authors: Jordan J. Feld, Wendy C. King, Marc G. Ghany, Kyong-Mi Chang, Norah Terrault, Robert P. Perrillo, Mandana Khalili, Amanda S. Hinerman, Harry LA. Janssen, Anna S. Lok
Journal: Clinical Gastroenterology and Hepatology (2022)
DNA base editing in nuclear and organellar genomes
Authors: Junjie Tan, Joachim Forner, Daniel Karcher, Ralph Bock
Journal: Trends in Genetics (2022)

Genome editing continues to revolutionize biological research. Due to its simplicity and flexibility, CRISPR/Cas-based editing has become the preferred technology in most systems. Cas nucleases tolerate fusion to large protein domains, thus allowing combination of their DNA recognition properties with new enzymatic activities. Fusion to nucleoside deaminase or reverse transcriptase domains has produced base editors and prime editors that, instead of generating double-strand breaks in the target sequence, induce site-specific alterations of single (or a few adjacent) nucleotides. The availability of protein-only genome editing reagents based on transcription activator-like effectors has enabled the extension of base editing to the genomes of chloroplasts and mitochondria. In this review, we summarize currently available base editing methods for nuclear and organellar genomes. We highlight recent advances with improving precision, specificity, and efficiency and discuss current limitations and future challenges. We also provide a brief overview of applications in agricultural biotechnology and gene therapy.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2020)

Biomarkers 0.0 0.2 0.4 0.6 BB-Downregulated genes (TOA diagnosticity z-score) 0.0 0.2 0.4 0.6 BB-Upregulated genes (TOA diagnosticity z-score) Epithelial Mesenchymal ** 2 1.5 1 0.5 0 -0.5 -1 -1.5 -2 Snail/Slug NF-κB AP-1 EGR1 SMAD CREB
Highlights from Recent Cancer Literature
Journal: Cancer Research (2020)

An Unexpected Prosurvival Function for Caspase-8Caspase-8 is a key apoptotic mediator and its expression is lost in many tumor types.Paradoxically, caspase-8 is highly expressed in a subset of tumors.M€ uller and colleagues identified a novel prosurvival function for nuclear caspase-8 that facilitates bypass of a p53dependent G 2 -M checkpoint.Expression of caspase-8 in the nucleus was associated with a poor prognosis and therapeutic resistance.DNA damage increased nuclear caspase-8, and caspase-8 knockdown enhanced p53-dependent apoptosis during the G 2 -M phase.Nuclear caspase-8 led to p53 degradation through cleavage of the p53 deubiquitinase, USP28, preventing apoptosis and allowing progression through G 2 -M.
Editorial Board and Contents
Authors: Joseph Napier, Guillaume De Lafontaine, Melissa Chipman, Erin Hahn, Alicia Grealy, Marina Alexander, Clare Holleley, Troy Day, Peter Abrams, Jan Kozłowski, Oskar Burger, Maciej Jan, Dan ´ko, George Williams, Jacob Moorad, Daniel Promislow, Jonathan Silvertown, David Keith, Bianca Dunker, Don Driscoll, Driscoll Keith, Russell Miller, Ryan Tangney, Neal Enright, Joseph Fontaine, David Merritt, Mark Ooi, Katinka Ruthrof, Ben Miller, Dakota Mccoy, David Haig, Matthias Schleuning, Lena Eike, Jörg Neuschulz, Irene Albrecht, Diana Bender, D Bowler, Susanne Dehling, Christian Fritz, Thomas Hof, Larissa Mueller, Marjorie Nowak, Katrin Sorensen, W Böhning-Gaese, Andrea Stephens, Jessica Miles, Margriet Ten Napel, Patrick Scheffmann, Göran Arnqvist, Spencer Barrett, Ragan Callaway, Stephen Carpenter, James Clark, Paul Craze, Rodolfo Dirzo, Andrew Dobson, Michael Donoghue, Douglas Erwin, Stephen Jackson, Christian Körner, Robert Lanfear, William Laurance, Georgina Mace, Harold Mooney, Randolph Nesse, Samir Okasha, Sarah Otto, Linda Partridge, Andrew Read, Rebecca Safran, Christine Simon, William Sutherland, Boris Worm, Eike Lena
Journal: Trends in Ecology & Evolution (2020)